Deletion of 12-lipoxygenase normalizes platelet function after storage and transfusion in thrombocytopenic mice

Objective Platelets for transfusion are stored for 5-7 days. During storage, platelets undergo numerous detrimental functional changes. In the current study, we sought to understand how genetic deletion of 12 –lipoxygenase (12-LOX) affects platelets during storage, before, and after transfusion. Approach and Results We obtained platelets from wild-type (WT) and 12-LOX-/-mice and performed storage studies for 24 and 48 hours. Using LC-MS/MS-MRM, we showed that ω-3 and ω-6 fatty acids increased significantly in stored platelets from 12-LOX-/-mice, while oxylipins were significantly lower than in WT platelets. The circulation time of fresh 12-LOX-/-platelets was significantly shorter than that of fresh WT platelets, but no differences were observed after storage. Baseline αIIbβ 3 integrin activation was significantly lower before and after 24 hours of storage in 12-LOX-/-platelets than in WT platelets. Surprisingly, after transfusion, we observed more baseline αIIbβ3 integrin activation in 12-LOX-/-platelets than in WT platelets. In line with this, transfusion of stored 12-LOX-/-platelets led to more frequent and significantly faster vessel occlusions than transfusion of stored WT platelets in a FeCl 3 -induced carotid artery injury model in thrombocytopenic mice. Conclusion Deleting 12-LOX improves the post-transfusion function of stored murine platelets. Pharmacologic inhibition of 12-LOX or dietary alterations of ω-3 and ω-6 PUFAs could significantly enhance human platelet quality and function after storage. Future studies must determine the feasibility and safety of 12-LOX inhibition in stored and transfused human platelets.